@article{3108128,
    title = "Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial",
    author = "Townsend, R.R. and Mahfoud, F. and Kandzari, D.E. and Kario, K. and Pocock, S. and Weber, M.A. and Ewen, S. and Tsioufis, K. and Tousoulis, D. and Sharp, A.S.P. and Watkinson, A.F. and Schmieder, R.E. and Schmid, A. and Choi, J.W. and East, C. and Walton, A. and Hopper, I. and Cohen, D.L. and Wilensky, R. and Lee, D.P. and Ma, A. and Devireddy, C.M. and Lea, J.P. and Lurz, P.C. and Fengler, K. and Davies, J. and Chapman, N. and Cohen, S.A. and DeBruin, V. and Fahy, M. and Jones, D.E. and Rothman, M. and Böhm, M. and Aoki, J. and Batson, B. and Dangas, G. and David, S. and Patel, M. and Patel, K. and Singh, J. and Weber, T. and Weil, J. and Zeller, T. and Ziada, K. and Tanabe, K. and Wilkins, R. and Contreras, J. and Steigerwalt, S. and Reedus, D. and Hoshide, S. and Svetkey, L. and Rao, A. and Brown, A. and Suppan, M. and Agdirlioglu, T. and Noory, E. and Chasen, C. and SPYRAL HTN-OFF MED trial investigators* and SPYRAL HTN-OFF MED trial investigators*",
    journal = "The Lancet Neurology",
    year = "2017",
    volume = "390",
    number = "10108",
    pages = "2160-2170",
    publisher = "The Lancet Publishing Group",
    doi = "10.1016/S0140-6736(17)32281-X",
    keywords = "antihypertensive agent;  antihypertensive agent, adult;  Article;  Australia;  Austria;  caregiver;  controlled study;  diastolic blood pressure;  drug surveillance program;  drug withdrawal;  Europe;  female;  follow up;  Germany;  Greece;  human;  hypertension;  intention to treat analysis;  Japan;  kidney angiography;  kidney denervation;  major clinical study;  male;  medication compliance;  middle aged;  multicenter study;  patient compliance;  patient safety;  priority journal;  randomized controlled trial;  single blind procedure;  systolic blood pressure;  therapy effect;  United Kingdom;  United States;  age;  aged;  blood pressure measurement;  catheter ablation;  clinical trial;  drug resistance;  hypertension;  international cooperation;  procedures;  prognosis;  reference value;  risk assessment;  severity of illness index;  sex factor;  sympathectomy;  treatment outcome, Adult;  Age Factors;  Aged;  Antihypertensive Agents;  Australia;  Blood Pressure Determination;  Catheter Ablation;  Drug Resistance;  Europe;  Female;  Humans;  Hypertension;  Internationality;  Male;  Middle Aged;  Patient Safety;  Prognosis;  Reference Values;  Risk Assessment;  Severity of Illness Index;  Sex Factors;  Single-Blind Method;  Sympathectomy;  Treatment Outcome;  United States",
    abstract = "Background Previous randomised renal denervation studies did not show consistent efficacy in reducing blood pressure. The objective of our study was to evaluate the effect of renal denervation on blood pressure in the absence of antihypertensive medications. Methods SPYRAL HTN-OFF MED was a multicentre, international, single-blind, randomised, sham-controlled, proof-of-concept trial. Patients were enrolled at 21 centres in the USA, Europe, Japan, and Australia. Eligible patients were drug-naive or discontinued their antihypertensive medications. Patients with an office systolic blood pressure (SBP) of 150 mm Hg or greater and less than 180 mm Hg, office diastolic blood pressure (DBP) of 90 mm Hg or greater, and a mean 24-h ambulatory SBP of 140 mm Hg or greater and less than 170 mm Hg at second screening underwent renal angiography and were randomly assigned to renal denervation or sham control. Patients, caregivers, and those assessing blood pressure were blinded to randomisation assignments. The primary endpoint, change in 24-h blood pressure at 3 months, was compared between groups. Drug surveillance was done to ensure patient compliance with absence of antihypertensive medication. The primary analysis was done in the intention-to-treat population. Safety events were assessed at 3 months. This study is registered with ClinicalTrials.gov, number NCT02439749. Findings Between June 25, 2015, and Jan 30, 2017, 353 patients were screened. 80 patients were randomly assigned to renal denervation (n=38) or sham control (n=42) and followed up for 3 months. Office and 24-h ambulatory blood pressure decreased significantly from baseline to 3 months in the renal denervation group: 24-h SBP −5·5 mm Hg (95% CI −9·1 to −2·0; p=0·0031), 24-h DBP −4·8 mm Hg (−7·0 to −2·6; p<0·0001), office SBP −10·0 mm Hg (−15·1 to −4·9; p=0·0004), and office DBP −5·3 mm Hg (−7·8 to −2·7; p=0·0002). No significant changes were seen in the sham-control group: 24-h SBP −0·5 mm Hg (95% CI −3·9 to 2·9; p=0·7644), 24-h DBP −0·4 mm Hg (−2·2 to 1·4; p=0·6448), office SBP −2·3 mm Hg (−6·1 to 1·6; p=0·2381), and office DBP −0·3 mm Hg (−2·9 to 2·2; p=0·8052). The mean difference between the groups favoured renal denervation for 3-month change in both office and 24-h blood pressure from baseline: 24-h SBP −5·0 mm Hg (95% CI −9·9 to −0·2; p=0·0414), 24-h DBP −4·4 mm Hg (−7·2 to −1·6; p=0·0024), office SBP −7·7 mm Hg (−14·0 to −1·5; p=0·0155), and office DBP −4·9 mm Hg (−8·5 to −1·4; p=0·0077). Baseline-adjusted analyses showed similar findings. There were no major adverse events in either group. Interpretation Results from SPYRAL HTN-OFF MED provide biological proof of principle for the blood-pressure-lowering efficacy of renal denervation. Funding Medtronic. © 2017 Elsevier Ltd"
}